In the latest issue of Proceedings of the National Academy of Sciences, Rao et aldemonstrate a fascinating, and probably immensely useful, application of genetic modification. They altered human commensal strain of E. coli to excrete proteins that prevent HIV from infecting immune cells.

This isn't the first time bacteria have been genetically modified to carry antigens, antibodies, or, as in the present example, peptides that directly interfere with a pathogen's mode of infection. But it is particularly interesting because the authors chose as a delivery strain a bug that is available as an over the counter probiotic supplement used to treat irritable bowel disease, cholitis, and Crohn's Disease. The strain, "Nissle 1917", has thus already been demonstrated safe for use in humans, and is distributed in capsules intended for oral ingestion that can be easily manufactured and then stored at room temperature.

It's important to note that while this paper shows the bacterium prevents HIV infection in cell culture, and that the bacterium survives in the intestines of mice while secreting "inhibitory concentrations of the anti-HIV peptide onto mucosal surfaces of the gastrointestinal tract", it does not actually demonstrate prevention of infection in an animal model, let alone humans. This experiment will no doubt require considerable review by institutional committees, and perhaps by the NIH itself (which is likely, since the work took place at the National Institute of Allergy and Infectious Disease).

Nonetheless, this is a quite sophisticated application of biological technology to address human needs. The anti-HIV peptide is itself a synthetic product, being a fusion of hemolysin-A and a fragment of gp-41, the later chosen because it binds to the protein complex on HIV that enables it to dock with and then enter human cells. Hemolysin-A served as the "shipping tag"; it is part of a protein excretion system already present in E. coli. Thus this work demonstrates the modification of a bacterial strain -- one already known to be well tolerated in humans -- by exploiting an extant protein export system to excrete a synthetic protein cargo that may provide significant protection against HIV.

Like Jay Keasling's work to manufacture anti-malarial drugs in E. coli, Rao et al are on the path to producing organisms that can be easily and inexpensively grown in culture, followed by harvest and packaging of therapeutic compounds or of the bugs themselves. This production work is similar to commercial efforts in India, China, and other developing countries, and helps pave the way to distributed biological manufacturing(PDF). There is clearly lots of work left to do before humans are given genetically modified bacteria as preventative microbicides, but the world it is achangin'.